We have observed that polysomes isolated from the frontal cortex of AD cases exhibit lower protein synthetic activity. The reduced activity appears to be due to inhibition of both the initiation and elongation steps, which has been characterized for various cells under a number of stresses. We propose that the reduction in polysome function is regulated by alterations in the phosphorylation of specific proteins known to modulate protein synthesis. The investigation will directly assay the phosphorylation states in control and AD postmortem tissues of various initiation factors with immunoblots and ribosomal protein S6. In addition, endogenous kinase and phosphatase activities affecting eIF-2a, S6, tRNA synthetases, and other proteins in the polysome fraction will be compared in the two tissues. The goal of the investigation will be to identify differences in protein phosphorylations that are associated specifically with protein synthesis in the AD tissues.